Method for selective thermal treatment

ABSTRACT

Methods for selective cooling or heating of a target site in the human body include a catheter having a supply elongated element and a delivery elongated element, with inlet and exit ports. Blood is withdrawn from the supply elongated element and cooled or heated in a control unit. The treated blood is sent to the targeted area via delivery elongated element. The supply elongated element can act as an insulator for the treated blood in the delivery elongated element.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 11/338,892, filed on Jan. 25, 2006, which is a continuation-in-partof U.S. patent application Ser. No. 11/041,701, filed on Jan. 25, 2005,both of which applications are incorporated by reference herein in theirentirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to methods for selectively treating atarget site in the body, specifically by changing a temperature thereof,and without significantly affecting other parts of the body.

It is generally known that many disease states and injuries respondfavorably to the application of heat and/or cold. For example,hypothermia, i.e. cooling, can reduce blood flow, inflammation andedema, and may alter a variety of effects of ischemia. On the cellularlevel, hypothermia and hyperthermia (heating) have the ability to effectmetabolic and enzymatic activity, reactive oxidant production and geneexpression. A number of experimental studies of ischemic stroke haveshown that hypothermia reduces the extent of neurologic damage andimproves neurologic function.

Prior art methods to effect hypothermia or hyperthermia have a number ofdisadvantages. Most of these methods primarily involve the entire bodyby employing surface techniques or systemic intravascular perfusion.U.S. Pat. No. 5,624,392 to Saab and U.S. Pat. No. 6,033,383 to Ginsburgteach the use of heat transfer catheters that are placed into the venousside of the vascular system. These devices cool or heat venous bloodpassing over them, and the heated or cooled blood is distributedthroughout the entire body. Such methods have serious limitations. Forexample, systemic hypothermia causes shivering, which increases themetabolic rate and may cause serious disturbances of the cardiovascularsystem. Surface techniques are slow, have limited heating/coolingcapability, and require apparatus that can interfere with the ability toperform a medical procedure. In addition, none of these prior arttechniques have the ability to control changes in blood flow andpressure that can result from the application of hypothermia orhyperthermia, nor do they have means to administer pharmacologic agentsselectively to the target area.

Other prior art methods designed to selectively treat an area withoutadversely affecting the rest of the body have been disclosed. Forexample, U.S. Pat. Nos. 6,436,071 and 6,605,106 to Schwartz teach acatheter for intravascular corporeal cooling, designed to eliminateproblems that develop due to complications from high pressure within adelivery catheter. This disclosure teaches the use of a pressure reliefvalve, which has the disadvantage of a likelihood of total body coolingupon activation of the valve. Additionally, long-term effects of thedisclosed system can include potential local vascular damage, andadditional total body cooling, since arterial blood passing over thecooling catheter would itself be cooled. U.S. Pat. No. 6,042,559 toDobak teaches a method and apparatus for performing hypothermia withoutsignificant effect on surrounding organs or other tissues. The disclosedapparatus includes a flexible supply catheter, and a separate flexibledelivery catheter—one used for removing the blood and one used fordelivering cooled blood into an artery feeding the selected organ. Thedelivery catheter has a layer of insulation. However, the use of twocatheters increases the risk of vascular complications, the complexityof the procedure, and the time to effect cooling of the target organ.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a method for selective thermal treatment which isdevoid of the above limitations.

SUMMARY OF THE INVENTION

According to one aspect of the invention there is provided a method forselectively cooling or heating a part of a body. The method includesproviding a device for insertion into a vessel, the device having afirst lumen and an exit port, a second lumen and a second port, whereinthe second lumen is positioned coaxial to the first lumen, and anocclusion element positioned between the exit port and the second port,inserting the device into a vessel, expanding the occlusion element soas to separate between a first area in fluid communication with the exitport and a second area in fluid communication with the second port,withdrawing normothermic blood from the second area via the second portand through the second lumen, delivering the normothermic blood to acontrol unit, thermally treating the normothermic blood in the controlunit to obtain thermally treated blood, and delivering the thermallytreated blood to the first area via the first lumen and the exit port.

According to yet another aspect of the invention there is provided amethod for insulating thermally treated blood for delivery to a locationin the body. The method includes providing a delivery catheter having adelivery lumen and a supply lumen which is coaxial to the deliverylumen, inserting the delivery catheter into the arterial system,withdrawing normothermic blood from the arterial system via the supplylumen, simultaneously providing thermally treated blood via the deliverylumen to the arterial system, the simultaneous providing being in alocation which is distal to a location of the withdrawing, wherein thewithdrawing is done coaxial to the simultaneous providing thermallytreated blood, thus providing a layer of insulation to the thermallytreated blood.

According to yet another aspect of the invention there is provided amethod for positioning of a thermal treatment catheter in a targetartery. The method includes positioning a guidewire in a proximal arterywhich is proximal to the target artery, introducing a search catheterover the guidewire, partially withdrawing the guidewire, locating thetarget artery with the search catheter, advancing the guidewire throughthe search catheter and into the target artery, removing the searchcatheter, and advancing a distal end of the thermal treatment catheterover the guidewire into the target artery.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1A is an illustration of a system including a catheter and acontrol unit, in accordance with one embodiment of the presentinvention;

FIG. 1B is an illustration of a system including a catheter and acontrol unit, in accordance with another embodiment of the presentinvention;

FIG. 2 is a schematic illustration of the control unit of the systems ofFIGS. 1A and 1B;

FIG. 3 is an illustration of a catheter in accordance with anotherembodiment of the present invention;

FIGS. 4A, 4B and 4C are illustrations of several embodiments of a distalportion of the catheters of FIG. 1A, FIG. 1B and FIG. 3, having distalends which are variably positionable;

FIGS. 5A-5C are illustrations of a catheter having a bendable distalend, in accordance with one embodiment of the present invention;

FIG. 6 is an illustration of a catheter which is suitable for anchoringin a separate vessel in accordance with one embodiment of the presentinvention;

FIGS. 7A-7C are illustrations of a distal portion of a catheter which issuitable for anchoring in a separate vessel, in accordance with anotherembodiment of the present invention;

FIGS. 8A-8H are illustrations of the steps of a method of positioning acatheter in a vessel in accordance with embodiments of the presentinvention;

FIGS. 9A-9H are illustrations of the steps of a method of positioning acatheter in a vessel in accordance with additional embodiments of thepresent invention;

FIGS. 10A-10F are illustrations of the steps of a method of positioninga catheter in a vessel in accordance with yet additional embodiments ofthe present invention;

FIGS. 11A-11C are illustrations of the steps of a method for treating aspecific target site in accordance with one embodiment of the presentinvention;

FIGS. 12A-12C are illustrations of a method for treating a specifictarget site in accordance with another embodiment of the presentinvention; and

FIGS. 13A-13C are illustrations of a method for treating a specifictarget site in accordance with yet another embodiment of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is of systems and methods which can be used forselective thermal therapy. Specifically, the present invention can beused to selectively cool or heat a specific organ in the body, using asingle catheter for collection and delivery of normothermic andthermally altered blood.

The principles and operation of systems and methods according to thepresent invention may be better understood with reference to thedrawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now to the drawings, FIGS. 1A and 1B illustrate a system 10for selective cooling or heating of an organ, in accordance withpreferred embodiments of the present invention. System 10 includes acatheter 12 and a control unit 14. Catheter 12 has a proximal end 16 anda distal end 18, and includes a supply elongated element 20 having asupply lumen 120 therethrough and a delivery elongated element 22 havinga delivery lumen 122 therethrough. Delivery elongated element 22 ispreferably an elongated tubular member, extending through an entirelength of catheter 12, from proximal end 16 to distal end 18, and has anexit port 24 at or near distal end 18 for delivery of blood to a targetsite. Supply elongated element 20 is preferably an elongated tubularmember which is positioned coaxially with respect to delivery elongatedelement 22, as shown in cross-section A-A, and extends from proximal end16 of catheter 12 to an area proximal to distal end 18. In analternative embodiment, supply elongated element 20 runs alongsidedelivery elongated element 22. In one embodiment, as shown in FIG. 1A,supply elongated element 20 has inlet ports 26 at one or more locationsalong its length, for receiving normothermic blood from the bloodvessel. In a preferred embodiment, as shown in FIG. 1B, supply elongatedelement 20 has an inlet port 26 located at a distal end 21 thereof. Inthis embodiment, inlet port 26 is created by the coaxial arrangement ofsupply elongated element 20 and delivery elongated element 22, whereinan inner diameter of supply elongated element 20 is sized at least 0.1mm greater than an outer diameter of delivery elongated element 22. Thespace created by this difference in diameter creates a port which issufficiently sized for receiving supply blood from the vessel, as willbe described in greater detail hereinbelow. In a preferred embodiment,an outer diameter of delivery elongated element 22 is in a range of0.081 inches to 0.128 inches and an inner diameter of supply elongatedelement 20 is in a range of 0.100 inches to 0.162 inches.

As shown in FIGS. 1A and 1B, at least one occlusion element 28 ispositioned at or near distal end 18 of catheter 12, proximal to exitport 24 and distal to a distal end 21 of supply elongated element 20. Ahub 30 for connecting supply elongated element 20 and delivery elongatedelement 22 to control unit 14 is located at proximal end 16 of catheter12. Hub 30 includes an inlet connector 32 for providing supply blood toa supply blood inlet 34 in control unit 14, and an outlet connector 36for receiving delivery blood from a delivery blood outlet 38 in controlunit 14. Control unit 14 thermally alters (i.e. heats or cools)normothermic blood received from supply blood inlet 34, and sends thethermally altered blood out through delivery blood outlet 38. Catheter12 can be introduced over a guidewire, either as an over-the-wire systemor as a rapid exchange system, or may include a fixed wire at its distaltip. In a preferred embodiment, delivery elongated element 22 acts as aguidewire lumen as well. In alternative embodiments, a separateguidewire lumen is positioned alongside or coaxial with deliveryelongated element 22. In the fixed-wire configuration, catheter 12 couldfurther include a torqueable catheter shaft. In one embodiment, such asthe one depicted in FIG. 1B, delivery elongated element 22 and supplyelongated element 20 are detachable from and/or movable with respect toone another.

The general cycle of blood flow is as follows. Normothermic blood,depicted by unbroken arrows 44, flows from a blood vessel, through atleast one inlet port 26, and into supply elongated element 20. Supplyelongated element 20 delivers the normothermic blood to control unit 14via inlet connector 32. Blood is then thermally altered in control unit14. Delivery elongated element 22 receives thermally altered blood,depicted by broken arrows 46, from delivery blood outlet 38 in controlunit 14 via outlet connector 36, and delivers the thermally alteredblood to the target site in the body. In order to ensure that heating orcooling of the target site is accomplished without causing heating orcooling of other parts of the body, it is necessary to physicallyseparate the collection of normothermic blood from the delivery ofthermally altered blood. In order to accomplish this separation using asingle device, catheter 12 is designed with both a supply elongatedelement and a delivery elongated element having an occlusion element 28for separation of blood inflow and outflow. By placing occlusion element28 between distal end 21 of supply elongated element 20 and exit port24, only the blood proximal to occlusion element 28 enters supply lumen120, and the thermally altered blood only reaches that part of thearterial system which is distal to occlusion element 28.

Reference is now made to FIG. 2, which is a schematic illustration ofcontrol unit 14 in greater detail. Control unit 14 includes supply bloodinlet 34 for receiving normothermic blood, depicted by unbroken arrow44, and delivery blood outlet 38 for delivering thermally altered blood,depicted by broken arrow 46. Control unit 14 further includes a thermaladjustor 40 for changing a temperature of normothermic blood receivedfrom supply blood inlet 34, thus producing thermally altered blood.Thermal adjustor 40 can be a heating mechanism, a cooling mechanism, ora combination heating/cooling mechanism which is controllable by a user.In a preferred embodiment, thermal adjustor 40 is a cooling mechanismsuch as, for example, Medtronic, Inc.'s Bio-Cal® Blood TemperatureControl Module or the MYOthermXP® Cardioplegia System. Alternatively,thermal adjustor 40 comprises a coiled tubing in an ice bath. In apreferred embodiment, control unit 14 further includes a pumpingmechanism 42 to facilitate delivery of thermally altered blood throughdelivery blood outlet 38. Pumping mechanism 42 can be, for example, acentrifugal blood pump (Bio-Pump®, Medtronic, Inc.; Sarns™ CentrifugalSystem, Terumo Cardiovascular Systems) or an electromagnetic pump(Levitronix® CentriMag® Blood Pumping System, Levitronix GmbH). In oneembodiment, control unit 14 further comprises a vacuum to assist inwithdrawal of the normothermic blood.

In order to more closely monitor physiological parameters during aprocedure, sensors 50 may be placed at or near exit port 24, shownschematically in FIGS. 1A and 1B. Sensors 50 can include one or severalsensors, capable of measuring pressure, temperature, flow, or acombination thereof. In an alternative embodiment, pressure is measuredby providing an additional lumen referred to as a pressure lumen. Thepressure lumen has a proximal pressure transducer attached thereto whichis capable of measuring the pressure of a column of fluid located withinthe pressure lumen. Sensors 50 are in communication with control unit 14via conventional wires 51 or via wireless communication. As shown inFIG. 2, control unit 14 can further include a processor 53 for receivingand processing signals from sensors 50 and providing an output based onthe processed signals. Output can be sent to a display 57, whichprovides output information to a user. The user can make a decisionbased on this output information regarding further adjustments of thetemperature, flow and pressure. Display 57 can be, for example, avisual, audio, numeric or any other suitable display. When a user seesthe display, he/she can manually adjust thermal adjustor 40. The usercan also decide to immediately stop the procedure if necessary.Alternatively, processor 53 sends output directly to thermal adjustor40, which then automatically changes cooling or heating parameters basedon the output.

In one embodiment, hub 30 further includes an infusion port 52, as shownin FIGS. 1A and 1B. Infusion port 52 can be used, for example, tointroduce contrast media to the site. Alternatively, infusion port 52can be used to introduce drugs. For example, lytic agents which aretypically used to dissolve clots can be introduced via infusion port 52into an artery, rather than the common practice of intravenous deliveryof these agents. Alternatively, in some circumstances it may bedesirable to introduce clotting agents, which can be done via infusionport 52. It should be readily apparent that any suitable agent,compound, drug, or substance can be introduced via infusion port 52, andall of these possibilities are included within the scope of the presentinvention.

Occlusion element 28 is comprised of an atraumatic surface so as not todamage the inner walls of a blood vessel. In a preferred embodiment,occlusion element 28 has a hydrophilic surface, which by attractingwater forms a natural atraumatic layer. Furthermore, a hydrophilicsurface can provide means for occlusion which is configured to open whenin contact with water components from the blood. Occlusion element 28may further include a coating for providing long-term (measured inhours, days or even months) implantation of catheter 12 in the body.Alternatively or in addition, occlusion element 28 may further include adrug coating. In one embodiment, occlusion element 28 is a balloon, suchas is commonly used with catheter systems, and is expandable byintroduction of a fluid therein, wherein the fluid can be a liquid or agas. In this embodiment, a separate inflation lumen is included withincatheter 12, either alongside or coaxial with delivery elongated element22, and is in fluid communication with occlusion element 28. Fluid isintroduced via an inflation port (not shown) positioned at hub 30. Thesetypes of balloons and inflation lumens are commonly known in the art.The balloon may be elastomeric, compliant, semi-compliant ornon-compliant, as long as it serves to occlude the vessel withoutcausing damage to the internal walls. In one embodiment, the balloon ispre-formed and relatively thin, so as to reduce the pressure necessaryto inflate the balloon, while keeping the outer diameter to a minimum.For example, balloon thickness may range from 0.0001 inches to 0.001inches, a range which is smaller than thicknesses of standard occlusionballoons.

In another embodiment, occlusion element 28 is a self-expanding elementconfined within a retractable sheath, such that upon retraction of thesheath, the self expanding element expands to a diameter sufficient toocclude the vessel. In this embodiment, the sheath is connected to aretractor positioned at proximal end 16 of catheter 12. Theself-expanding element may be comprised of an elastic or spring-likematerial, or a shape-memory alloy. Such materials are known in the art.In another embodiment, occlusion element 28 is a mechanically actuatedmechanism, whereby it is expanded by mechanical means. In yet anotherembodiment, occlusion element 28 is comprised of a temperature sensitivematerial which can be expanded or retracted by exposure to specifictemperatures. Specifically, perfusion of cooled or heated blood throughdelivery lumen 122 would cause expansion of occlusion element 28, andperfusion of normothermic blood through delivery lumen 122 (such as, forexample, during renormalization of temperature) would cause retractionof occlusion element 28. This may be accomplished, for example, by usinga shape-memory material, either as occlusion element 28 itself, or as anactuator positioned alongside occlusion element 28. Similarly, thiscould be accomplished by using a bi-metallic strip. In one embodiment,occlusion element 28 is an integral part of the catheter, wherein aportion of catheter 12 having a slightly wider diameter is configured tobe wedged into the vessel, and thus acts as occlusion element 28,providing both occlusion and anchoring functionality.

Occlusion element 28 further includes a radiopaque marker 48 for viewingof a location of catheter 12 generally and occlusion element 28specifically within the vessel. In one embodiment, occlusion element 28is itself comprised of radiopaque material. In alternative embodiments,one or more radiopaque markers 48 are positioned on occlusion element28. Additional radiopaque markers 48 may also be positioned in otherplaces along catheter 12 such as, for example, at distal end 18, or atinlet ports 26. In one embodiment, a radiopaque marker 48 is positionedat the distal tip of catheter 12. Radioapaque marker 48 can be a ringsurrounding the distal tip, or, in order to minimize stiffness at thetip, a radiopaque marker 49 (shown in FIG. 1B) may be comprised of asmall sliver of radiopaque material embedded within a portion of thedistal tip. In one embodiment, radiopaque marker 48 is filled with anadhesive and positioned so as to seal an inflation lumen for inflationof occlusion element 28.

Reference is now made to FIG. 3, which is an illustration of a catheter12 in accordance with another embodiment of the present invention.Catheter 12 is similar in construction to catheter 12 shown in FIGS. 1Aand 1B, with an additional feature of an auxiliary delivery elongatedelement 23, preferably situated between supply elongated element 20 anddelivery elongated element 22. Auxiliary delivery elongated element 23is preferably an elongated tubular member having an auxiliary lumen 123therethrough, and is configured to receive a supplemental blood flowfrom control unit 14 (shown in FIGS. 1A and 1B) and to deliver thesupplemental blood (depicted by wide arrows 48) to a vessel. In oneembodiment, the supplemental blood is taken from the control unit 14 andintroduced into auxiliary delivery elongated element 23 at an initialthermally altered temperature. Supplemental blood as depicted by widearrows 48 undergoes a temperature change during its flow from theproximal end to the distal end of auxiliary delivery elongated elementdue to conduction from the normothermic blood in the blood vessel whichis in close proximity thereto. In this embodiment, the temperature ofsupplemental blood that exits ports 25 of auxiliary delivery elongatedelement 23 is of a different temperature T₂ than the temperature T₁ ofthe thermally altered blood depicted by broken arrows 46, which isdelivered to the target site. The presence of an additional layer ofblood flow in a lumen surrounding delivery elongated element 22 providesincreased insulation for the thermally altered blood being delivered tothe target site. Furthermore, blood from auxiliary delivery elongatedelement 23 can be used for simultaneous treatment of different parts ofthe body. Thus, for example, if it were desired to treat the target sitewith one temperature and an additional site with another temperature,auxiliary delivery elongated element 23 could be used for treatment ofthe additional site. The amount of temperature change that occurs withinauxiliary delivery lumen 123 depends on the flow rate and the initialtemperature difference between the thermally altered blood enteringauxiliary delivery lumen 123 and the normothermic blood surroundingauxiliary delivery elongated element 23.

In a preferred embodiment, auxiliary delivery elongated element 23 iscoaxially arranged with respect to delivery elongated element 22, andincludes at least one secondary exit port 25, preferably in a distalportion thereof. In an alternative embodiment, exit port 25 isconfigured similar to inlet port 26 as depicted in FIG. 1B, wherein anexit port 25 is created by the coaxial arrangement of auxiliary deliveryelongated element 23 and delivery elongated element 22, wherein an innerdiameter of auxiliary delivery elongated element 23 is sized at least0.1 mm greater than an outer diameter of delivery elongated element 22.The space created by this difference in diameter is sufficient fordelivering supply blood to the vessel. The distal portion of auxiliarydelivery elongated element 23 is proximal to exit port 24. Supplyelongated element 20 is positioned coaxially with respect to auxiliarydelivery elongated element 23, and distal end 21 of supply elongatedelement 20 is proximal to secondary exit ports 25. In one embodiment,supply elongated element 20 is a standard vascular sheath and may have aside arm 27 from which normothermic blood is sent to control unit 14. Inanother embodiment, supply elongated element 20 is an extended sheath,and may extend to 100 cm or more depending on the application.

A second occlusion element 54 may be positioned proximal to secondaryexit ports 25 and distal to inlet ports 26 of supply elongated element20. In this way, a first target site is supplied by thermally alteredblood exiting delivery elongated element 22 and having a temperature T₁,and a second target site is separately supplied by supplemental bloodexiting auxiliary delivery elongated element 23 and having a temperatureT₂.

Reference is now made to FIGS. 4A-4C, which are illustrations of adistal portion of catheter 12, in accordance with another embodiment ofthe present invention, wherein exit port 24 is positionable at varyingdistances from ports 61. Ports 61 are inlet or outlet ports of a coaxialelongated element 60, which can be any elongated element coaxial todelivery elongated element 22. In one embodiment, coaxial elongatedelement 60 is a supply elongated element and ports 61 are inlet ports.In another embodiment, coaxial elongated element 60 is an auxiliarydelivery elongated element, and ports 61 are secondary exit ports.Delivery elongated element 22 is movable within coaxial elongatedelement 60. Movement can be a twisting motion, for example, whereindelivery elongated element 22 and coaxial elongated element 60 areattached with a bellows 56, as shown in FIG. 4A. Alternatively, movementcan be a sliding motion, wherein delivery elongated element 22 andcoaxial elongated element 60 are attached via telescoping means 58, asshown in FIG. 4B. In a preferred embodiment, movement is achieved bycoaxial arrangement of coaxial elongated element 60 and deliveryelongated element 22, as shown in FIG. 4C. In this arrangement, deliveryelongated element 22 can be variably positioned within coaxial elongatedelement 20. Thus, a length of delivery elongated element 22 may protrudeproximal to the proximal end of catheter 12. In this case, it may benecessary to include an adjustable anchor 63 for anchoring the proximalportion of delivery elongated element 22 to the body or surgical drapeof the patient. Alternatively, a length of supply elongated element 20may protrude proximal to the proximal end of catheter 12. In this case,it may be necessary to include an adjustable anchor for anchoring theproximal portion of supply elongated element 20 to the body or surgicaldrape of the patient. These configurations allow for the tip of catheter12 to be positioned as desired, without concern for the resultinglocation of the proximal end. Any suitable adjustable anchor means maybe used, including, for example, a luer lock, a gland, a squeeze-lockmechanism, etc. Any other means for changing a distance between exitport 24 and ports 61 is included within the scope of the invention.

In some instances, it may be desirable to anchor catheter 12 into avessel, providing greater control and easier accessibility to the targetsite. Reference is now made to FIGS. 5A-5C, which are illustrations of acatheter having a bendable distal end 18 for anchoring. As shown in FIG.5A, catheter 12 includes delivery elongated element 22 and occlusionelement 28. At least one exit port 24 is located distal to occlusionelement 28. In one embodiment, exit port 24 is at distal end 18 ofcatheter 12. In another embodiment, exit port 24 is located anywherebetween occlusion element 28 and distal end 18. In one embodiment,distal end 18 is initially in a straightened positioned as it isadvanced over a guidewire 62. Guidewire 62 is insertable throughdelivery lumen 122. Alternatively, guidewire 62 may be insertablethrough a separate guidewire lumen (not shown), which is either coaxialwith or adjacent to delivery lumen 122. Catheter 12 is advanced overguidewire 62 until a desired location is reached. Guidewire 62 is thenremoved, allowing catheter 12 to assume a bent configuration, asdepicted in FIG. 5B. The bent configuration is suitable for anchoring ina vessel, as shown schematically in FIG. 5C. In an alternativeembodiment, catheter 12 has a fixed wire at its distal end, and distalend 18 is initially straightened by inserting a removable stylet. Oncethe desired location is reached, the stylet is removed, causing distalend 18 to assume its bent configuration. In one embodiment, distal end18 is comprised of a shape memory alloy.

Alternatively, it may be desirable to anchor catheter 12 in a vesselother than the one leading to the target site. For example, if catheter12 is anchored in a branch vessel, thermally altered blood can bediverted into the main vessel by strategically placing exit port 24 at aspecific location or locations.

Reference is now made to FIG. 6, which is an illustration of catheter 12suitable for anchoring in a separate vessel, in accordance with oneembodiment of the present invention. Catheter 12 has a closed distal end18 and an exit port 24 located along its shaft, proximal to distal end18. Catheter 12 further includes at least two occlusion elements: firstocclusion element 28, which is positioned between exit port 24 and ports61 of coaxial elongated element 60, and distal occlusion element 55,which is positioned between exit port 24 and distal end 18 of catheter12. Coaxial elongated element 60 and ports 61 can be supply elongatedelement 20 with inlet ports 26, or auxiliary delivery elongated element23 and secondary exit ports 25. First occlusion element 28 is designedto separate an area for receiving thermally altered blood (i.e. thetarget site) from an area supplying normothermic blood to control unit14, or from an area receiving supplemental blood at a differenttemperature T₂. Distal occlusion element 55 is designed to act as ananchor, while also separating an area for receiving thermally alteredblood (the target site) from an untreated area. In a preferredembodiment, first and distal occlusion elements 28 and 55 includeradiopaque markers 48 for allowing for positioning of catheter 12 withinthe blood vessel.

Reference is now made to FIGS. 7A and 7B, which are illustrations of adistal portion of catheter 12, suitable for anchoring in a separatevessel, in accordance with another embodiment of the present invention.As shown in FIG. 7A, guidewire 62 is introducible through deliveryelongated element 22. In an alternative embodiment, catheter 12 includesa separate guidewire elongated element (not shown) either coaxial withor alongside delivery elongated element 22. Catheter 12 includes adistal occlusion element 55, which in one embodiment is an inflatableballoon designed to extend over distal end 18 upon inflation. As shownin FIG. 7B, inflation of distal occlusion element 55 results inexpansion of the balloon over distal end 18, causing the delivery lumento be sealed. This type of configuration can be accomplished, forexample, by attaching the balloon to the catheter shaft near the distalend of the catheter, such that upon inflation, the balloon is configuredto expand over the edge of catheter 12. Alternatively, distal occlusionelement 55 can have multiple attachment points 57, as shown in FIG. 7Cin a deflated state, which dictate a direction of expansion for distalocclusion element 55. Exit port 24 is located on the shaft of catheter12, and is positioned proximal to distal occlusion element 55.

It should be readily apparent that in all of the described embodiments,additional lumens may be included for various purposes. For example, alumen for oxygenation of blood may be added. Additional cooling/heatinglumens or additional lumens to control flow or pressure may be added aswell.

In a preferred embodiment, system 10 is used to provide hypothermia fortreatment of stroke. A target temperature for cooling is in the range of18 to 30 degrees Celsius, and may be maintained for hours or days. Thesystem described herein also allows for gradual rewarming of the treatedarea by slowly introducing blood of different temperatures.

Introduction and positioning of catheter 12 into a selected vessel inthe body can be accomplished in various ways. Reference is now made toFIGS. 8A-8H, which are schematic illustrations of a method ofpositioning catheter 12 in a selected vessel in the body. In theembodiment shown, catheter 12 is positioned in the left internal carotidartery. However, it should be readily apparent that catheter 12 mayalternatively be positioned in the right or left common carotidarteries, or any of the internal or external carotid arteries based onthe target location. Initially, an incision or puncture is made at aperipheral location, typically the femoral artery, although otherlocations such as the brachial or radial artery, for example, can beused as well. A guidewire 162 is inserted through the incision and intothe vessel, in this case, femoral artery 200, as shown in FIG. 8A.Optionally, as shown in FIG. 8B, a vascular sheath 202 with a dilatorportion is introduced over guidewire 162. Vascular sheaths and dilatorsare commonly known in the art, and are commonly used for providingvascular access to catheters. Once the sheath is in place, the dilatoris removed, and a search catheter 204 is introduced over guidewire 162,as shown in FIG. 8C. Search catheter 204 can be, for example, a guidingcatheter or an angiography catheter, both of which are types ofcatheters known in the art, and which include a tip which is pre-shapedin various configurations, suitable for selecting particular vessels.While search catheter 204 is positioned over guidewire 162, the tip ofsearch catheter 204 is relatively straight. Search catheter 204 andguidewire 162 are advanced together through arterial system and into theaortic arch 210, as shown in FIG. 8D. Guidewire 162 is pulled backproximally, which allows for search catheter 204 to assume its bentconfiguration, suitable for selecting a specific vessel. Search catheter204 is then used to locate the left common carotid artery 212, as shownin FIG. 8E. Search catheter 204 may alternatively be used to locate theright common carotid artery 214. Guidewire 162 is then advanced intoleft common carotid artery 212, as shown in FIG. 8F. Search catheter 204is removed, and guidewire 162 may be advanced further into the leftinternal carotid artery 218, as shown in FIG. 8G. Alternatively,guidewire 162 may be advanced into an external carotid artery 216, ormay remain in the common carotid artery 212, depending on the targetedarea. Catheter 12 of the present invention is then introduced overguidewire 162, with the tip of delivery elongated element 22 positionedwithin the selected vessel, in this case left internal carotid artery218 as shown in FIG. 8H. Supply elongated element 20 preferably remainswithin aortic arch 210. This method can be used for a catheter 12 inaccordance with any of the described embodiments above.

Reference is now made to FIGS. 9A-9H, which are schematic illustrationsof the steps of an alternative method of introduction and positioning ofcatheter 12 into a selected vessel in the body. In this method, anincision or puncture is made as described above, and a long guidewire164 is introduced into the vessel, in this case, femoral artery 200, asshown in FIG. 9A. Supply elongated element 20, which in at least oneembodiment described above (see for example, FIG. 1B) is detachable fromthe rest of catheter 12, is introduced over guidewire 164, as shown inFIG. 9B. A removable dilator 166 is positioned within supply elongatedelement 20 to facilitate percutaneous introduction. Supply elongatedelement 20 is advanced, either with the removable dilator in place orafter the removable dilator has been removed, until supply elongatedelement 20 is in a position within aortic arch 210 proximal to the leftcommon carotid artery 212, as shown in FIG. 9C. If the dilator had notpreviously been removed, at this point the dilator is removed. Searchcatheter 204 is then introduced through supply elongated element 20, asshown in FIG. 9D. Guidewire 164 is pulled back proximally, which allowsfor search catheter 204 to assume its bent configuration, suitable forselecting a specific vessel. Search catheter 204 is then used to locatethe left common carotid artery 212, as shown in FIG. 9E. Search catheter204 may alternatively be used to locate the right common carotid artery214. Guidewire 164 is then advanced into left common carotid artery 212,as shown in FIG. 9F. Search catheter 204 is removed, and guidewire 164may be advanced further into the left external carotid artery 216, asshown in FIG. 9G. Alternatively, guidewire 164 may be advanced into aninternal carotid artery 218, or may remain in the common carotid artery212, depending on the desired target. Remaining portions of catheter 12which are not yet in the vessel are then introduced over guidewire 164,with the tip of delivery elongated element 22 positioned within theselected vessel, in this case left external carotid artery 216. Supplyelongated element 20 preferably remains within aortic arch 210. Thislast step creates assembly of catheter 12 within the desired location.

Reference is now made to FIGS. 10A-10F which are schematic illustrationsof the steps of an alternative method of introduction and positioning ofcatheter 12 into a selected vessel in the body. In this embodiment, anincision or puncture is made as described above, and a long guidewire164 is introduced into the vessel, as shown in FIG. 10A. A dilator 168is positioned within delivery elongated element 22, and catheter 12 withdilator 168 in place is advanced over guidewire 164, as shown in FIG.10B. Catheter 12 and dilator 168 are advanced over guidewire 164 intoaortic arch 210, as shown in FIG. 10C. When catheter 12 is in positionin aortic arch 210, dilator 168 is removed, and a search catheter 224may then be introduced though delivery elongated element 22, as shown inFIG. 10D. Search catheter 224 is sized to fit within delivery elongatedelement 22. Alternatively, delivery elongated element 22 may itself beconfigured with a bent configuration for selecting a vessel, and thusmay be used as a search catheter. Guidewire 164 is pulled backproximally, and search catheter 224 or bent delivery elongated element22 is used to locate the left common carotid artery 212, as shown inFIG. 10E. Search catheter 224 or bent delivery elongated element 22 mayalternatively be used to locate the right common carotid artery 214.Guidewire 164 is then advanced into left common carotid artery 212, asshown in FIG. 10F. Search catheter 224 is removed, and guidewire 164 maybe advanced further into the left external carotid artery 216.Alternatively, guidewire 164 may be advanced into an internal carotidartery 218, or may remain in the common carotid artery 212, depending onthe targeted area of the brain. Catheter 12 is advanced into left commoncarotid artery 212, with the tip of delivery elongated element 22positioned within the selected vessel, in this case left externalcarotid artery 216. Supply elongated element 20 preferably remainswithin aortic arch 210. For this embodiment, it may be necessary forsupply elongated element 20 to have a tapered distal end so as to avoiddamage of the vessel during insertion. If inlet ports are positionedalong supply elongated element 20, as in FIG. 1A, the distal end 21 ofsupply elongated element 20 can be tapered by design. If inlet port 26is located at the distal end 21 of supply elongated element 20, as shownin FIG. 1B, a temporary tapering element can be included at distal end21. For example, an inflatable balloon may be positioned at distal end21 of supply elongated element 20, so that during insertion, the ballooncan be inflated, providing a tapered edge, and during collection ofsupply blood, the balloon can be deflated for blood collection.

In all of the described embodiments, positioning of supply elongatedelement 20 within the vessel should be such that supply blood iscollected from retrograde flow of blood. Thus, it is preferable not toadvance the supply elongated element 20 into the common carotid artery.Rather, supply elongated element 20 (or at least the inlet ports 26 fromsupply elongated element 20) should remain in the aorta. If supplyelongated element 20 and delivery elongated element 22 are notdetachable from one another, supply elongated element 20 may be sized(lengthwise) so as to avoid its entry into the carotid artery.Alternatively, if supply elongated element 20 and delivery elongatedelement 22 are detachable, a marker on the distal end of supplyelongated element 20 may aid in this positioning. In alternativeembodiments, catheter 12 may be placed in other locations in the bodydepending on the desired target area. For example, a renal artery can betargeted to provide cooling/heating to a kidney, or a coronary arterycan be targeted to provide cooling/heating to a heart.

Reference is now made to FIGS. 11A-C, which are illustrations of amethod for treating a specific target site in accordance with apreferred embodiment of the present invention. As shown in FIG. 11A,catheter 12 is inserted into a blood vessel, and advanced to a vesselwhich is in fluid communication with the target site, referred tohereinafter as adjacent vessel 100. In a preferred embodiment, whereinthe goal is to selectively cool the brain without induction of systemichypothermia, the target site is the brain, and vessel 100 is the carotidartery (right or left, common, internal or external). A position ofcatheter 12 within vessel 100 is monitored by visualization ofradiopaque marker 48. When catheter 12 is in the desired location,occlusion element 28 is expanded, as shown in FIG. 11B. This expansionprimarily serves to isolate a particular section of adjacent vessel 100which leads to the target site, thereby preventing normothermal bloodfrom flowing into the target organ, and can also help anchor catheter 12in place. Reference is now made to FIG. 11C, which illustrates the flowof blood. Once occlusion element 28 is deployed, normothermic blood,represented by arrows 44, enters supply elongated element 20 via inletports 26. It should be readily apparent that although the methoddepicted in FIGS. 11A-11C shows supply elongated element 20 havingmultiple inlet ports and positioned in a vessel in such a way so as tocollect antegrade blood, these depictions should not be regarded aslimiting. In alternative embodiments, as described above with referenceto FIGS. 1B, 8H and 9H, supply elongated element 20 may have one inletport, and it may be positioned within the aortic arch. Normothermicblood flows through supply lumen 120, out through inlet connector 32 ofhub 30 and through supply blood inlet 34 into control unit 14. Controlunit 14 then heats or cools the blood to form thermally altered blood,which is pumped out through delivery blood outlet 38, through outletconnector 36, and into delivery elongated element 22. Thermally alteredblood, represented by broken arrow 46, flows out through exit port 24and into the portion of the blood vessel which leads to the target site.In one embodiment, pharmaceuticals are simultaneously administered tothe target site via drug infusion port 52. In another embodiment,sensors located at or near the exit ports measure physiologicalparameters such as pressure, flow and temperature, and the data is sentto control unit 14. Control unit 14 compares the received data todesired settings and adjusts heating/cooling as required. This cycle cancontinue for as long as is necessary for the particular application. Ina preferred embodiment, the cycle is repeated for 1-72 hours.

Reference is now made to FIGS. 12A-C, which are illustrations of amethod for treating a specific target site in accordance with anotherembodiment of the present invention. As shown in FIG. 12A, catheter 12is inserted into a blood vessel, and advanced to a vessel which is influid communication with the target site, referred to hereinafter asadjacent vessel 100. In a preferred embodiment, wherein the goal is toselectively cool the brain without induction of systemic hypothermia,the target site is the brain, and vessel 100 is the carotid artery(right or left, common, internal or external). A position of catheter 12within vessel 100 is monitored by visualization of radiopaque marker 48.When catheter 12 is in the desired location, occlusion element 28 andsecond occlusion element 54 are both expanded, as shown in FIG. 12B.Occlusion element 28 and second occlusion element 54 can be sequentiallyor simultaneously expanded. Expansion of occlusion element 28 primarilyserves to isolate a particular section of blood vessel 100 which leadsto the target site, and can also help anchor catheter 12 in place.Expansion of second occlusion element 54 serves to separate an area fordelivery of supplemental blood, which is of a different temperature T₂than a temperature T₁ of thermally treated blood sent to the targetsite, and from normothermic blood returning through supply elongatedelement 20. Reference is now made to FIG. 12C, which illustrates theflow of blood. Once occlusion element 28 and second occlusion element 54are deployed, normothermic blood, represented by arrows 44, enterssupply elongated element 20 via inlet ports 26. It should be readilyapparent that although the method depicted in FIGS. 12A-12C shows supplyelongated element 20 having multiple inlet ports and positioned in avessel in such a way so as to collect antegrade blood, these depictionsshould not be regarded as limiting. In alternative embodiments, asdescribed above with reference to FIGS. 1B, 8H and 9H, supply elongatedelement 20 may have one inlet port, and it may be positioned within theaortic arch. Normothermic blood flows through supply lumen 120, outthrough inlet connector 32 of hub 30 and through supply blood inlet 34into control unit 14. Control unit 14 then heats or cools the blood toform thermally altered blood, which is pumped out through delivery bloodoutlet 38, through outlet connector 36 and into delivery elongatedelement 22. Thermally altered blood, represented by broken arrow 46,flows out through exit port 24 and into the portion of the blood vesselwhich leads to the target site. In addition, supplemental blood,represented by wide arrows 48, is sent through auxiliary deliveryelongated element 23 and into a secondary vessel 101, which may lead toa secondary target site. In one embodiment, pharmaceuticals aresimultaneously administered to the target site and/or to thesupplemental blood via drug infusion port 52. In another embodiment,sensors located at or near the exit ports measure physiologicalparameters such as pressure, flow and temperature, and the data is sentto control unit 14. Control unit 14 compares the received data todesired settings and adjusts heating/cooling as required. This cycle cancontinue for as long as is necessary for the particular application.

Reference is now made to FIGS. 13A-C, which are illustrations of amethod for treating a specific target site in accordance with yetanother embodiment of the present invention. As shown in FIG. 13A,catheter 12 is inserted into a blood vessel, and advanced to a secondaryvessel 101 which is near vessel 100. For example, vessel 100 andsecondary vessel 101 can be branches of a main vessel. This method maybe desirable, for example, if vessel 100 is diseased and might beadversely affected by introduction of a foreign element such as acatheter therein. In a preferred embodiment, wherein the goal is toselectively cool the brain without induction of systemic hypothermia,the target site is the brain, and secondary vessel 101 is the carotidartery (right or left, common, internal or external). A position ofcatheter 12 within vessel 101 is monitored by radiopaque marker 48. Whencatheter 12 is in the desired location, occlusion element 28 and distalocclusion element 55 are expanded, as shown in FIG. 13B. Expansion ofocclusion elements 28 and 55 serves to isolate blood vessel 100 whichleads to the target site, and anchors catheter 12 in place withoutplacing catheter 12 directly in blood vessel 100. Reference is now madeto FIG. 13C, which illustrates the flow of blood. Once occlusionelements 28 and 55 are deployed, normothermic blood, represented byarrows 44, enters supply elongated element 20 via inlet ports 26. Itshould be readily apparent that although the method depicted in FIGS.12A-12C shows supply elongated element 20 having multiple inlet portsand positioned in a vessel in such a way so as to collect antegradeblood, these depictions should not be regarded as limiting. Inalternative embodiments, as described above with reference to FIGS. 1B,8H and 9H, supply elongated element 20 may have one inlet port, and itmay be positioned within the aortic arch. Normothermic blood flowsthrough supply lumen 120, out through inlet connector 32 of hub 30 andthrough supply blood inlet 34 into control unit 14. Control unit 14 thenheats or cools the blood to form thermally altered blood, which ispumped out through delivery blood outlet 38, through outlet connector36, and into delivery elongated element 22. Thermally altered blood,represented by broken arrow 46, flows out through exit port 24 and intothe portion of the blood vessel which leads to the target site. In oneembodiment, pharmaceuticals are simultaneously administered to thetarget site via drug infusion port. In another embodiment, sensorslocated at or near the exit ports measure physiological parameters suchas pressure, flow and temperature, and the data is sent to control unit14. Control unit 14 compares the received data to desired settings andadjusts heating/cooling as required. This cycle can continue for as longas is necessary for the particular application.

It should be readily apparent that a single catheter serves to bothcollect and deliver the normothermic and thermally altered blood. In anadditional embodiment, all or some blood contact surfaces can be coatedwith an anti thrombotic substance such as heparin.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. A method for selectively cooling or heating a part of a body, themethod comprising: providing a device for insertion into a vessel, thedevice comprising a first lumen and an exit port, a second lumen and asecond port, said second lumen positioned coaxial to said first lumenand extending along a majority of a length of said first lumen, and anocclusion element positioned between said exit port and said secondport; inserting said device into a vessel; expanding said occlusionelement so as to separate between a first area in fluid communicationwith said exit port and a second area in fluid communication with saidsecond port; withdrawing normothermic blood from said second area viasaid second port and through said second lumen; delivering saidnormothermic blood to a control unit; thermally treating saidnormothermic blood in said control unit to obtain thermally treatedblood; and delivering said thermally treated blood to said first areavia said first lumen and said exit port.
 2. The method of claim 1,wherein said thermally treating comprises cooling.
 3. The method ofclaim 1, wherein said thermally treating comprises heating.
 4. Themethod of claim 1, wherein said delivering said thermally treated bloodcomprises pumping said thermally treated blood.
 5. The method of claim1, further comprising delivering a second thermally treated blood to alocation in the body, said second thermally treated blood having adifferent temperature than said thermally treated blood.
 6. The methodof claim 1, further comprising monitoring a physiological parameter; andadjusting said thermally treating based on said monitored parameter. 7.A method for insulating thermally treated blood for delivery to alocation in the body, the method comprising: providing a deliverycatheter having a delivery lumen and a supply lumen which is coaxial tosaid delivery lumen; inserting said delivery catheter into the arterialsystem; withdrawing normothermic blood from the arterial system via saidsupply lumen; simultaneously providing thermally treated blood via saiddelivery lumen to the arterial system, said simultaneous providing beingin a location which is distal to a location of said withdrawing, whereinsaid withdrawing is done coaxial to said providing thermally treatedblood, thus providing a layer of insulation to said thermally treatedblood.
 8. The method of claim 1, wherein said providing a devicecomprises: positioning a guidewire in a proximal artery, said proximalartery being proximal to the target artery; introducing a searchcatheter over said guidewire; partially withdrawing said guidewire;locating the target artery with said search catheter; advancing saidguidewire through said search catheter and into the target artery;removing the search catheter; and advancing a distal end of said deviceover the guidewire into the target artery.
 9. The method of claim 8,wherein said target artery is a carotid artery, and wherein saidadvancing comprises advancing into the carotid artery.
 10. The method ofclaim 8, wherein said target artery is a renal artery, and wherein saidadvancing comprises advancing into the renal artery.
 11. The method ofclaim 8, wherein said target artery is a coronary artery, and whereinsaid advancing comprises advancing into the coronary artery.
 12. Themethod of claim 8, further comprising introducing a supply elongatedelement over said guidewire, and wherein said introducing said searchcatheter is done through a lumen of said supply elongated element. 13.The method of claim 8, wherein said positioning comprises positioning inan aortic arch.
 14. The method of claim 8, wherein said introducing asearch catheter includes introducing a search catheter through adelivery elongated element of said thermal treatment catheter.
 15. Themethod of claim 8, wherein said introducing a search catheter includesintroducing a delivery elongated element of said thermal treatmentcatheter, wherein said delivery elongated element has a bent distal endfor locating a vessel.
 16. The method of claim 8, wherein said advancingsaid guidewire through said search catheter and into the carotid arteryincludes advancing said guidewire into an external carotid artery, andadvancing a distal end of said treatment catheter into the carotidartery includes advancing said distal end into the external carotidartery.
 17. The method of claim 8, wherein said advancing said guidewirethrough said search catheter and into the carotid artery includesadvancing said guidewire into an internal carotid artery, and advancinga distal end of said treatment catheter into the carotid artery includesadvancing said distal end into the internal carotid artery.